TOXIC CHEMICAL INFLUENCES ON REPRODUCTION IN VIVO & IN VITRO(MONKEYS,MICE,HAMSTER

有毒化学物质对体内繁殖的影响

• 批准号: 3855723
• 负责人: W RICHARD DUKELOW
• 金额: --
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855723
• 关键词: Saimiri; acrosome; benzene; carbon tetrachloride; cell differentiation; cell growth regulation; cytotoxicity; early embryonic stage; embryo /fetus toxicology; environmental contamination; environmental toxicology; fertility; fertilization; hamsters; laboratory mouse; membrane permeability; methylene chloride; sperm capacitation; toluene; trichloroethylene; water pollution

The proposed studies will examine the specific mechanisms of action of selected groundwater contaminates (benzene, trichloroethene, 1,1,1- trichloroethane, methylene chloride, carbon tetrachloride, and toluene) on the basic mechanisms of action relative to the reproductive process. These studies will build on an existing research program and will utilize in vitro methods of cell and tissue culture and employ the in vitro fertilization process. Since some of the in vitro methods proposed are applied for the first time in toxicity studies, additionally in vivo assay methods will be conducted to verify the in vitro findings. Several of these proposed test chemicals have been implicated in the reproductive dysfunction in occupationally exposed workers, yet little is known about the etiology. Some known interactions between these chemicals and the cellular functions in other organs suggest that they may interrupt the processes of reproduction by altering the permeability of cellular membrane, depression of calcium pump, or inhibit glycolysis and cell proliferation. It has also been hypothesized that these chemicals selectively inhibit the proliferation of cells at certain stages of development, while allow the growth of less differentiated ones. The in vitro methods developed or modified in our laboratories will be used to study the processes of sperm capacitation, the acrosome reaction, sperm and egg fusion, and embryonic development, which normal function require scheduled biochemical and structural changes of cellular membranes. Studies will also be conducted to compare the cytoxicity of these chemicals in embryonic cells before and after the initiation of differentiation, i.e. before and after the compaction. These results will not only aid in determining the exact effects of the chemicals on gametes and embryonic cells, they will also have important implications relative to the chemicals' ability in interrupting intercellular communication signals in other tissues.

拟议的研究将探讨具体的作用机制 选定的地下水污染物（苯、三氯乙烯、1,1,1- 三氯乙烷、二氯甲烷、四氯化碳、甲苯） 与生殖过程相关的基本作用机制。 这些研究将建立在现有研究计划的基础上，并将利用 细胞和组织培养的体外方法，并采用体外 受精过程。由于提出的一些体外方法是 首次应用于毒性研究以及体内研究 将进行测定方法来验证体外研究结果。 其中一些拟议的测试化学品与 职业暴露工人的生殖功能障碍，但很少有 了解病因。这些化学物质之间的一些已知相互作用 其他器官的细胞功能表明它们可能 通过改变渗透性来中断繁殖过程 细胞膜，钙泵抑制，或抑制糖酵解和 细胞增殖。人们还假设这些化学物质 选择性地抑制细胞在某些阶段的增殖 发展，同时允许差异较小的个体生长。在 我们实验室开发或修改的体外方法将用于 研究精子获能过程、顶体反应、精子 以及卵子融合和胚胎发育，这是正常功能所需要的 细胞膜的预定生化和结构变化。 还将进行研究来比较这些药物的细胞毒性 胚胎细胞在启动之前和之后的化学物质 差异，即压实之前和之后。这些结果将 不仅有助于确定化学物质对配子的确切影响 和胚胎细胞，它们也将具有重要的相关意义 化学物质中断细胞间通讯的能力 其他组织中的信号。